Lungwena Antenatal Intervention Study. A Single-centre Intervention Trial in Rural Malawi, Testing Maternal and Infant Health Effects of Presumptive Intermittent Treatment of Pregnant Women With Sulfadoxine-pyrimethamine and Azithromycin
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,320
- 试验地点
- 1
- 主要终点
- Proportion of preterm births
研究概览
简要总结
The purpose of this study is to examine whether treatment of pregnant Malawian women with repeated doses of sulfadoxine-pyrimethamine and azithromycin antibiotics will prevent preterm deliveries and result in other health benefits both for the mother and the foetus/newborn.
详细描述
Maternal anaemia, preterm deliveries and low birth weight are common in Sub-Saharan Africa and contribute significantly to the ill-health of pregnant women and infants. The present study is based on the assumption that these adverse outcomes can be prevented by improved antimicrobial management of malaria and sexually transmitted infections (STI) among pregnant women. To test the hypothesis, a randomised clinical trial following Good Clinical Practice (GCP) is being carried out in Malawi, South-Eastern Africa.
A total of 1320 consenting women who present at a rural antenatal clinic after 14 but before 26 completed gestation weeks will be enrolled. One third of the women will receive antenatal care according to national recommendations, including regular visits to health centre, screening for pregnancy complications, haematinic and vitamin A supplementation and two doses of presumptive malaria treatment with sulfadoxine-pyrimethamine. Another third will receive otherwise the same care, but sulfadoxine-pyrimethamine treatment is given at monthly intervals. The final third receives standard antenatal care, sulfadoxine-pyrimethamine treatment at monthly intervals and two doses of presumptive STI treatment with azithromycin. Women are monitored throughout pregnancy and delivery and newborn growth will be followed up for five years.
The primary outcome measure is proportion of preterm births in the three study groups. Secondary maternal outcomes include anaemia and malaria parasitaemia during pregnancy, at delivery and at 1, 3, and 6 months after delivery, gestational weight gain and morbidity and STI prevalence after delivery. Secondary child outcomes consist of proportion of babies with low birth weight, mean birth weight, growth in infancy and childhood, incidence of malnutrition in infancy and childhood, and mortality. Additionally, information is collected on the development of malaria-specific humoral immunity in pregnancy and participant experiences from the study. Participant safety is systematically monitored throughout the intervention.
There have been two edits two the trial protocol, since the original approval. In the first one, there was an amendment to follow child growth and mortality until and child development at 5 years of age, with visits at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months. In the second amendment, there was an addition to monitor child antropometrics, physical, mental, and social health at and mortality by 10-12 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Age >= 15 years
- •Ultrasound confirmed pregnancy
- •Quickening
- •Foetal age 14-26 gestation weeks
- •Maternal availability for follow-up during the entire study period
排除标准
- •Known maternal tuberculosis, diabetes, kidney disease or liver disease
- •Any severe acute illness warranting hospital referral at enrollment visit
- •Mental disorder that may affect comprehension of the study or success of follow-up
- •Twin pregnancy
- •Pregnancy complications evident at enrollment visit (moderate to severe oedema, blood hemoglobin [Hb] concentration < 50 g/l, systolic blood pressure [BP] > 160 mmHg or diastolic BP > 100 mmHg)
- •Prior receipt of azithromycin during this pregnancy
- •Receipt of sulfadoxine and pyrimethamine within 28 days of enrollment
- •Known allergy to drugs containing sulfonamides, macrolides or pyrimethamine
- •History of anaphylaxis
- •History of any serious allergic reaction to any substance, requiring emergency medical care
- •Concurrent participation in any other clinical trial
研究组 & 干预措施
Control
Standard antenatal care as described in intervention
干预措施: Sulfadoxine-pyrimethamine treatment twice during pregnancy (Drug)
Monthly SP
Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine, as described in intervention
干预措施: Sulfadoxine-pyrimethamine at 4-week intervals (Drug)
AZI-SP
Standard antenatal care + monthly intermittent presumptive treatment of malaria with sulfadoxine pyrimethamine + two presumptive treatments of sexually transmitted infections and malaria with azithromycin, as described in intervention
干预措施: Sulfadoxine-pyrimethamine every 4 weeks + azithromycin twice (Drug)
结局指标
主要结局
Proportion of preterm births
时间窗: once, after delivery
Proportion of babies who are born before 37 completed gestation weeks
Number of serious adverse events
时间窗: Cumulative during pregnancy and neonatal period
Death, life-threatening event, hospitalization, congenital anomaly, or any othe condition consedered an SAE by a study physician
次要结局
- Mean birth weight(Once, after delivery)
- Nutritional status(1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age)
- Motor development, Griffiths test, sub-score(5 years of age)
- Percentage of low birth weight babies(Once, after delivery)
- Mean duration of gestation(Once, after delivery)
- Percentage of low head circumference at birth(Once, after delivery)
- Infant mortality(Cumulative until 365 days of post-natal life)
- Percentage of women with peripheral blood malaria parasitaemia at 32 gestational weeks and at delivery(At enrolment, every 4 weeks thereafter and at delivery)
- Incidence of moderate underweight during infancy or childhood(Cumulative during infancy and childhood)
- Perinatal mortality(Cumulative until 7 days of post-natal life)
- Neonatal mortality(Cumulative until 28 days of post-natal life)
- Percentage of women with mild, moderate or severe anaemia at every antenatal visit and at 1, 3, and 6 months after delivery(Several antenatal and postnatal visits)
- Mean maternal blood haemoglobin concentration at each antenatal visit and at 1, 3, and 6 months after delivery(Several antenatal and postnatal visits)
- Maternal weight gain during pregnancy(Cumulative during pregnancy)
- Mean number of maternal illness days during pregnancy(Cumulative during pregnancy)
- Prevalence of maternal chlamydia trachomatis, neisseria gonorrhoea, and vaginal trichomoniasis infection at 4 weeks after delivery(At 4 weeks after delivery)
- Attained lenght / height(1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age)
- Attained weight(1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age)
- Attained head circumference(1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months and 10-12 years of age)
- Childhood mortality, % of subjects who have died by the 10-12 year follow-up visit(Cumulative incidence by 10-12 years of age)
- Social development, Griffiths test, sub-score(5 years of age)
- Diastolic blood pressure, mmHg(10-12 years of age)
- Cognitive development, Raven's colour matrix, score(10-12 years of age)
- Reaction time, milliseconds(10-12 years of age)
- Systolic blood pressure, mmHg(10-12 years of age)
- Central blood pressure, mmHg(10-12 years of age)
- Pulse rate, beats / minutes(10-12 years of age)
- Vascular resistance, mmHg·min/l(10-12 years of age)
- Lean body mass, expressed in kg, with one decimal(10-12 years of age)
- Fat mass, expressed in kg, with one decimal(10-12 years of age)
- Fat percentage, expressed proportion of body weight (per cent, with one decimal)(10-12 years of age)
- Self-rated well-being, score(10-12 years of age)
研究者
Per Ashorn
Professor of Pediatrics
Tampere University